Malaria is one of the world's most widespread infectious diseases. Ridley et al., 2002. Much effort is currently being devoted to develop effective vaccines to prevent humans from becoming infected with malaria parasites. LeBlanc et al., 2008; Troye-Blomberg et al., 2007. Treatment of humans afflicted with malaria with antimalarial amines, such as chloroquine, has been effective for over 50 years. Ridley et al., 2002. Malaria parasites, however, have developed widespread resistance to popular quinoline-based antimalarial drugs, including chloroquine. Olliaro et al., 2001. Such resistance seriously compromises the efficacy of chloroquine for treating people infected with malaria and has stimulated a search for new natural and synthetic antimalarial agents.
Progress in chemotherapeutic methods of treating humans afflicted with malaria has been made using protease inhibitors to starve the parasites, Hof et al., 2006; Pandey et al., 2004; using antimalarial acridones, Kelly et al., 2009, and new 4-aminoquinolines, Yearick et al., 2008, to counteract resistance; and using some modified chloroquine analogs. Ramanathan-Girish et al., 2004. A new non-quinoline family of rapidly acting antimalarial peroxides was discovered in China during the early 1970s and has since become popular in treating malaria in humans. Bégué and Bonnet-Delepon, 2007; Gelb, 2007; Haynes, 2006; Jefford, 2004; Klayman, 1985; O'Neill and Posner, 2004; Shizhen, 2003; Tang et al., 2004. The natural trioxane artemisinin and its semi-synthetic derivative trioxanes artemether and water-soluble sodium artesunate are now recommended by the World Health Organization (WHO) for use in combination with a classical antimalarial amine drug for reliable chemotherapy of humans infected with malaria. WHO, 2006. This artemisinin combination therapy (ACT) is now widely used in areas of the world where malaria is endemic. Ashley and White, 2005; de Pilla Varotti et al., 2008; Adjuik et al., 2004; Guthmann et al., 2006; Myint et al., 2007; Sirima et al., 2009.
Typically, current ACT requires a repeated dose regimen, which usually involves a total of three to six doses of a trioxane plus an amino antimalarial administered to a malaria-infected patient over several days. Sagara et al., 2008; Fanello et al., 2007. Patient compliance with adhering to such a repeated-dose regimen, however, is often a serious challenge. Souares et al., 2009. Patient compliance would be improved and cost lowered by a single dose oral cure. Therefore, a single-dose oral cure for malaria is highly desirable.